March 28, 1948.

Dr, Nile Fries,

Institute of Physiological Botany,
University of Uppsala,

Sweden.

Dear Nils,

Pirst, let us thank you for sending us that interesting brochure of photo-
graphs of Sweden. We enjoyed it very much. .

Since the Fall, of course, we have been installed here, and aust confess
to finding the move a good one. Our present labomatory facilities are ten-.
porary, while a remodelied space is being outfitted for permanent use, but
we have been able to accomplish a good deal nevertheless. Esther is enrolled
as a student, ani is working on the genetic control of mitability in "mtabile"
mutants of E. coli &12, while I have been occupied with a study of the gane-
enzyme relationship, using ultra-violet induced lactose-necgative atants as
material.

‘ What chemical work has been done poiate to the activity of a simple, single
lactose-hydrolysing enzyme in this organism, and I wish I could write that the
genetic control of this ensyme were simple, as one might expect on the "one~-to
~one” theory, but, alas it is not so. Some eight different loei are involved in
the two or three hundred lactose-negative amtants so far studied, and there may
be more. In coli K-12, at any rate, it locks like this enayme is subject to the
control of many genes. On the other hand, some of the mutations are apparently
pleiotropic, even on the ensymatic level, — single mutations affecting several
enzymea involved in carbohydbatebmetabolisa. Further chemical work may uncover
an inprobebly complex metabolic scheme that would vitiate these rexarks, but at
the moment 1 mst conelude that: the study of atations can give no certain
information on the nhyeical mechanisms of gene action. A sihgle gene may con-
fer specificity on a alngle enzyme, but it may also alter the ceil ebonomy in some
subtle way that 7 may prevent the appearance of other enzymes.

Of course, all this work has been on E. coli, and I am sure that everyone
would feel a lot hanpier to see a similar study on other organisas with a more
securely established sexual satage-~ anc I pepe propose to do this either with
Neurospora or with Ophiostoma. May 1 ask you now to send me som of your sore
vigorous wild type and mtantd@ strains. In particular have you paid any atten-
tion to the carbohydratebmetaboliem of Ophietoma 7 Do you know which sugars it
Gan utilize for growth, and what the most promiant astabolic products may be?
Have you made any attempt at enzyme studies in this fungus? Be sure to let us
know how you have been and what you ocoupy yourself with now. Father sends her
bess regards. . , ,

Yours sincerely,

Joshua Lederberg
Agsistant Professor of Genetics